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dc.contributor.authorHo, Duy-Khiet
dc.contributor.authorCosta, Ana
dc.contributor.authorde Rossi, Chiara
dc.contributor.authorde Souza Carvalho-Wodarz, Cristiane
dc.contributor.authorLoretz, Brigitta
dc.contributor.authorLehr, Claus-Michael
dc.date.accessioned2020-07-09T12:44:48Z
dc.date.available2020-07-09T12:44:48Z
dc.date.issued2018-02-21
dc.identifier.citationMol Pharm. 2018;15(3):1081-1096. doi:10.1021/acs.molpharmaceut.7b00967.en_US
dc.identifier.pmid29425049
dc.identifier.doi10.1021/acs.molpharmaceut.7b00967
dc.identifier.urihttp://hdl.handle.net/10033/622346
dc.description.abstractThe majority of the currently used and developed anti-infectives are poorly water-soluble molecules. The poor solubility might lead to limited bioavailability and pharmacological action of the drug. Novel pharmaceutical materials have thus been designed to solve those problems and improve drug delivery. In this study, we propose a facile method to produce submicrocarriers (sMCs) by electrostatic gelation of anionic ß-cyclodextrin (aß-CD) and chitosan. The average hydrodynamic size ranged from 400 to 900 nm by carefully adjusting polymer concentrations and N/C ratio. The distinct host-guest reaction of cyclodextrin derivative is considered as a good approach to enhance solubility, and prevent drug recrystallization, and thus was used to develop sMC to improve the controlled release profile of a poorly soluble and clinically relevant anti-infective ciprofloxacin. The optimal molar ratio of ciprofloxacin to aß-CD was found to be 1:1, which helped maximize encapsulation efficiency (∼90%) and loading capacity (∼9%) of ciprofloxacin loaded sMCs. Furthermore, to recommend the future application of the developed sMCs, the dependence of cell uptake on sMCs size (500, 700, and 900 nm) was investigated in vitro on dTHP-1 by both flow cytometry and confocal microscopy. The results demonstrate that, regardless of their size, an only comparatively small fraction of the sMCs were taken up by the macrophage-like cells, while most of the carriers were merely adsorbed to the cell surface after 2 h incubation. After continuing the incubation to reach 24 h, the majority of the sMCs were found intracellularly. However, the sMCs had been designed to release sufficient amount of drug within 24 h, and the subsequent phagocytosis of the carrier may be considered as an efficient pathway for its safe degradation and elimination. In summary, the developed sMC is a suitable system with promising perspectives recommended for pulmonary extracellular infection therapeutics.en_US
dc.language.isoenen_US
dc.publisherAmerican Chemical Societyen_US
dc.relationinfo:eu-repo/grantAgreement/H2020/ 724290en_US
dc.rightsopenAccessen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectchitosanen_US
dc.subjectciprofloxacinen_US
dc.subjectcyclodextrinen_US
dc.subjectdrug deliveryen_US
dc.subjectmacrophage uptakeen_US
dc.subjectpolysaccharideen_US
dc.subjectpulmonary deliveryen_US
dc.titlePolysaccharide Submicrocarrier for Improved Pulmonary Delivery of Poorly Soluble Anti-infective Ciprofloxacin: Preparation, Characterization, and Influence of Size on Cellular Uptake.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dc.identifier.eissn1543-8392
dc.contributor.departmentHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.en_US
dc.identifier.journalMolecular pharmaceuticsen_US
dc.source.volume15
dc.source.issue3
dc.source.beginpage1081
dc.source.endpage1096
refterms.dateFOA2020-07-09T12:44:50Z
dc.source.journaltitleMolecular pharmaceutics
dc.source.countryUnited States


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